This invention is generally in the field of (micro)containment/controlled release or exposure devices, and more particularly to implantable medical devices for the storage and controlled exposure or release of contents located in reservoirs in these devices, and applications therefor.
Undesirably, some drugs have limited solubility or undergo gelation at physiological pH. Certain phase changes of drugs can impede release from highly concentrated dosages. Such phase changes can be particularly problematic when controlling drug delivery in microenvironments. Examples of controlled delivery of drugs or other chemicals to microenvironments from implantable medical devices having microreservoirs is described in U.S. Pat. No. 5,797,898, U.S. Pat. No. 6,527,762, and U.S. Pat. No. 6,491,666, and U.S. Patent Application Publication No. 2004/0247671, all of which are incorporated by reference herein. In particular, certain types of drug formulations, such as concentrated lyophilized dosages and concentrated organic solvent solutions, tend to gel at the reservoir opening when exposed to physiological fluid and block, impede, or otherwise interfere with the release of drug from the implantable medical devices. For certain drugs this gelation is due to its limited solubility at physiological pH. For example, teriparatide, which is hPTH(1-34), has a limited solubility at physiological pH. Thus, when teriparatide is released from a drug delivery device and contacts physiological fluid, there is the potential for a precipitate or gel to form and adversely affect the drug's release.
It would be desirable to eliminate or compensate for unwanted gelation, aggregation, or precipitation of drugs or otherwise increase the delivery rate of the drugs so that drug release from reservoirs or other microcontainment devices is unimpeded and can properly controlled. In many instances, solid dosage forms are desired for their stability. It would further be desirable to improve delivery of drug formulations, particularly protein drugs, from implanted medical devices, particularly where the drug is stored in the devices as a solid or in concentrated, rather than dilute, solutions. It would also be desirable to decrease the time required for substantially all of a dose of a drug formulation to be released from a drug delivery device, where the drug is one requiring rapid delivery.